Transcobalamin-2 (TCN2)

Transcobalamin-2 (TCN2) is a plasma transporter protein that binds vitamin B12 (cobalamin) and delivers it from the bloodstream into the cell by binding to specific cell-surface receptors and promoting cellular uptake through endocytosis[1][5][7][9]. It has a critical role in supporting essential one-carbon metabolism, including DNA synthesis, methylation reactions, and homocysteine clearance, by ensuring adequate intracellular vitamin B12 for coenzyme activity[3][5]. Deficiency of TCN2, often due to rare genetic mutations, leads to defective cobalamin delivery, causing macrocytic or megaloblastic anemia, neurological deficits, and sometimes severe immunodeficiency[1][7][8]. The only known direct ligand is vitamin B12; no classic drug antagonists or inhibitors are reported. Biomarkers such as holotranscobalamin and TCN2 gene analysis are used for diagnosis, as deficiency is a medically actionable cause of severe disease in infancy and childhood[1][3][8].

Other names

Transcobalamin IITranscobalamin-2TC IITC-2TC2TCIIVitamin B12-binding protein 2macrocytic anemia proteinD22S676D22S750

Mediates cellular uptake of vitamin B12 via receptor-mediated endocytosis; drugs (vitamin B12 analogs) may use transport by binding TCN2[1][5][7][9]